Methamphetamine (MA) abuse has risen in recent years and in some regions is used more than cocaine. Despite this, little is known about its prenatal effects. During the first funding period we established that a third trimester equivalent exposure to high doses of MA in rats results in acoustic startle hyperreactivity and deficits and deficits in learning the Morris maze hidden platform test of spatial navigation. During the most recent funding, we extended these findings and determined that the spatial learning deficit is replicable, generalizable (found in 3 strains), obtained over a range of doses, specific to spatial navigation, and affects reference but not working memory. We also obtained pharmacokinetic data showing that P1-10 and P11-20 treatment produce similar absorption, peak and elimination patterns despite the fact that only P11-20 leads to spatial learning impairments. We also found that MA at these developmental ages does not induce hyperthermia or alter brain monoamines, but that it does dramatically increase plasma corticosterone. We now propose to pursue these findings with aims to determine the effects of MA at different developmental stages . For the third trimester equivalent exposure period we plan to examine MA's: (1) longitudinal effects on spatial learning, (2) strategic and motivational specificity, (3) dose-response effects, (4) critical period effects, (5) conditional place preference effects, (6) glucocorticoid and glucocorticoid receptor effects, and (7) NMDA receptor effects. For first and second trimester equivalent exposure periods we will determine MA's effects on: (8) spatial learning and memory (with controls material influences), and (8) glucocorticoids. These studies will advance our understanding of MA's effects on the developing brain neurochemically and functionally, especially MA's cognitive effects, and provide new information that may ultimately assist in extrapolating these findings to the risk infants and children may encounter when their mother's abuse MA during pregnancy.